Tyrosine kinases mediation of c-fos expression by cell swelling in cardiac myocytes.
We investigated the signal transduction mechanism initiated by hypotonic cell swelling in cardiac myocytes using c-fos expression as a nuclear marker. Treatment of myocytes with hypotonic culture media rapidly induced c-fos expression, whereas hypertonic stress had no effect on it. Extensive pharmacological studies indicated that only tyrosine kinase inhibitors suppressed the hypotonic swelling-induced c-fos expression; down-regulation of protein kinase C or a Ca2+ chelator (EGTA) had no effect. Hypotonic stress immediately (within 5s) increased tyrosine kinase activity. Thus tyrosine kinase is one of the earliest signaling molecules activated by hypotonic stress and plays an essential role in hypotonic swelling-induced c-fos expression. Rapid activation of tyrosine kinase may be a common early signaling mechanism in response to mechanical stresses that increase cell membrane tension.
Sadoshima
J
J
Cardiovascular Research Center, University of Michigan Medical Center, Ann Arbor 48109, USA.
Izumo
S
S
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004789:Enzyme Activation; D015870:Gene Expression; D017781:Genes, Immediate-Early; D016762:Genes, fos / Q000502:physiology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D009994:Osmolar Concentration; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D013314:Stress, Mechanical
D011505:Protein-Tyrosine Kinases